Adaptive (T and B Cells) Immunity and Control by Dendritic Cells in Atherosclerosis

Abstract

14 Altogether, these early observations on the presence of T cells in human and in mouse atherosclerotic plaques remained associative and did not show causation.Subsequent studies using animal models of atherosclerosis, especially Apoe -/-or Ldlr -/-mice, in which human-like atherosclerotic lesions develop spontaneously or in response to high-fat diet, provided more direct evidence for the participation of adaptive immunity in atherogenesis. Apoe -/-or Ldlr -/-mice crossed with immunodeficient mice that lack the V(D)J recombination-activating protein 1 (Rag1) or have a severe combined immunodeficiency mutation (SCID; scid/scid mice) show, in general, reduced development of atherosclerotic lesions when fed a chow diet.5 These immunodeficient mice that lack both T and conventional B cells are not particularly informative on the role of specific T-and B-cell subpopulations that can be either pro-or antiatherogenic (see below). One study found no difference between immune-competent and immune-deficient mice fed a high-fat diet. 15The specific role of T cells was substantiated by experiments showing that the transfer of CD4 + T cells into scid/scid/ Apoe -/-mice fully reversed the atheroprotection provided by T/B deficiency. 16 However, when the effect of CD4 + T cells was evaluated in CD4-deficient Apoe -/-mice, contrasting results were reported. Female CD4 -/-Apoe -/-mice exhibited markedly larger lesions in the descending thoracic aorta, but no effect was observed in the aortic root when compared with wild-type (WT) Apoe -/-mice. 17 Intriguingly, in a subsequent study using the same CD4/Apoe double knockout mice, atherosclerosis in the aortic sinus was reduced, but the authors made no mention of the effect of CD4 + T-cell deficiency on atherosclerosis in the aorta.18 Of note, in both studies, the CD8 + cell population and the titers of anti-malondialdehyde (MDA)-oxidized lowdensity lipoprotein (oxLDL) IgM antibodies were increased. CD8 + T cells were recently shown to promote the development of vulnerable atherosclerotic plaques, 19 whereas natural antioxLDL IgM autoantibodies are atheroprotective 20 (see below). The specific recognition of peptide antigens presented by MHC molecules triggers TCR signaling, but costimulatory and coinhibitory receptors on T cells direct T-cell function and determine T-cell fate. These cosignaling molecules are members of the immunoglobulin superfamily, including B7 (CD80/86), CD28, programmed cell death 1 and cytotoxic T-lymphocyte antigen 4 (CTLA4), and the tumor necrosis factor (TNF) receptor superfamily, including CD40, CD27, OX40, and CD137. Experiments aimed at investigating the role of cosignaling molecules provided further evidence for a role of T cells in atherogenesis 21,22 (see Functional roles for DCs in atherosclerosis section of this article). For example, blockade of the OX40-OX40L interaction by anti-OX40L antibody treatment in Ldlr -/-23 or Apoe -/-24 mice reduced atherosclerosis. Yet, blockade of T-cell activation was accompanied by an enhanced B-1 cell activity an...

Impact of Postprocedural TIMI Flow on Long-Term Clinical Outcomes in Patients with Acute Myocardial Infarction

“…Meanwhile, in case of HDL cholesterol, it could affect atherosclerosis which has been identified as an inflammatory process 40) driven by the adaptive (T and B cells) immune system and dendritic cells. 41) In our study, a rise of HDL cholesterol might be favorably associated with early inflammatory process for establishment of good coronary flow in STEMI patients. In addition, this study showed that the final coronary flow after PCI was better in LCX territory than in other treated arteries in NSTEMI (HR 0.544 [0.304-0.975], P = 0.001), even after the adjustment for the presence of other factors.…”

Changes of Naturally Occurring CD4⁺CD25⁺ FOXP3⁺ Regulatory T Cells in Patients With Acute Coronary Syndrome and the Beneficial Effects of Atorvastatin Treatment

“…7) The high degree of maturity of dendritic cells helps T cells differentiate toward the T-helper 1 lineage, and down-regulates the number of circulatory Tregs. 32) In addition, the differentiation of Tregs is influenced by cytokines including IL-10 and TGF-β 1 .…”

Possible Pivotal Role of Latent Chronic T. gondii Infection in the Pathogenesis of Atherosclerosis

“…Atherosclerotic lesions are characterized by progressive accumulation of lipids, macrophages, NK cells, T and B lymphocytes, smooth muscle cells, and fibroproliferative elements in the intima of arteries [12,13] . Functional analysis of different T-cell subsets role identified the T H 1 responses as proatherogenic, whereas T H 2 immune responses exert antiatherogenic actions [14,15] . Atherosclerosis is also associated with B-cell activation, and traditional T cell-driven B2 cells responses promote atherosclerosis, while innate B1 cells provide protective action through the secretion of naturally occurring antibodies [14,15] .…”

“…Functional analysis of different T-cell subsets role identified the T H 1 responses as proatherogenic, whereas T H 2 immune responses exert antiatherogenic actions [14,15] . Atherosclerosis is also associated with B-cell activation, and traditional T cell-driven B2 cells responses promote atherosclerosis, while innate B1 cells provide protective action through the secretion of naturally occurring antibodies [14,15] . Several authors have hypothesized that the number of different pathogens, including T. gondii [16] , may promote synergistic inflammatory responses that are capable of triggering and exacerbating atherosclerosis [17] .…”